Lack of CD44 variant 6 expression in rectal cancer invasive front associates with early recurrence

Table 1 Clinical characteristics of the patients n (%)

Clinical characteristics	Short course RT	Long course RT	Control	P1
Study population (n = 214)
Male	57 (63)	34 (64)	32 (45)	0.03
Female	33 (37)	19 (36)	39 (55)
Mean age (yr)	65.2	64.7	74.5	< 0.001
Preoperative T
T1-2	28 (31)	0 (0)	22 (31)
T3	54 (60)	2 (4)	12 (17)	< 0.001
2T4	1 (1)	50 (94)	3 (4)
Tx	7 (8)	1 (2)	34 (48)
Postoperative T
T1	3 (3)	2 (4)	5 (7)
T2	34 (38)	6 (11)	26 (37)
T3	50 (56)	27 (51)	37 (52)	< 0.001
T4	3 (3)	14 (26)	3 (4)
T0	0	4 (8)	0
Postoperative N
N0	53 (59)	36 (68)	41 (58)
N1	26 (29)	14 (26)	15 (21)	0.33
N2	11 (12)	3 (6)	12 (17)
Nx	0	0	3 (4)
Grade
G1	9 (10)	10 (19)	12 (17)
G2	58 (64)	33 (62)	48 (68)	0.07
G3	21 (23)	3 (6)	11 (16)
Gx	2 (2)	7 (13)	0
3Crm (mm)
0	3 (4)	11 (25)	4 (9)
0 ≤ crm ≤ 2	9 (12)	7 (16)	7 (16)	0.009
> 2	65 (84)	26 (59)	32 (74)
Disease specific outcome
Alive without recurrence	64 (71)	25 (47)	39 (55)
Alive with recurrence	7 (8)	7 (13)	4 (6)	0.07
Died of disease	11 (12)	12 (23)	18 (25)
Died of other causes	8 (9)	9 (17)	10 (14)

¹Differences between the three treatment groups using Fisher’s exact test; mean age with analysis of variance;

²Includes the T3 tumors with threatened circumferential margin involvement;

³Circumferential margin, data available in 164 cases. RT: Radiotherapy.

Table 2 Intratumoral staining pattern of membranous CD44 variant 6 expression related to treatment group and some clinicopathological variables n (%)

Variable (n = 177)	"Front-positive"(n = 105)	"Front-negative"(n = 72)	P1
Treatment group
Short-course RT	46 (44)	32 (44)
Long-course RT	24 (23)	14 (19)	0.87
Control	35 (33)	26 (36)
Postoperative T
T1-2	43 (41)	21 (29)
T3	55 (52)	42 (58)	0.19
T4	7 (7)	9 (13)
Postoperative N
N0	68 (65)	40 (56)
N1-2	36 (34)	31 (43)	0.37
Nx	1 (1)	1 (1)
2Crm
≤ 2 mm	14 (18)	22 (38)	0.01
> 2 mm	64 (82)	36 (62)
Tumor growth pattern
Expanding	63 (60)	23 (32)	< 0.001
Infiltrating	42 (40)	49 (68)
Disease-specific outcome
Alive without recurrence	68 (65)	39 (54)
Alive with recurrence	3 (3)	12 (17)	0.01
Died of disease	21 (20)	15 (21)
Died of other causes	13 (12)	6 (8)

¹Pearson χ²; P value for difference between “front-positive” and “front-negative” groups;

²Circumferential margin, data available in 136 out of 177 cases. RT: Radiotherapy.

Table 3 Results of multivariate analysis

Variable	DFS			DSS
	Adjusted HR	95% CI	P	Adjusted HR	95% CI	P
Sex
Female (ref)	1.0			1.0
Male	1.9	1.0-3.5	0.04	1.5	0.7-3.0	0.3
Age
< 70 yr (ref)	1.0			1.0
≥ 70 yr	1.4	0.8-2.4	0.3	4.7	2.1-10.5	< 0.001
Postoperative T
T1-2 (ref)	1.0			1.0
T3	3.2	1.4-7.2	0.005	2.0	0.8-5.1	0.1
T4	5.9	2.0-17.0	0.001	4.8	1.4-17.0	0.02
Postoperative N
N0 (ref)	1.0			1.0
N1-2, Nx	2.0	1.1-3.7	0.02	0.8	0.4-1.7	0.6
1Postoperative grade
G1 (ref)				1.0
G2				1.3	0.4-3.9	0.7
G3				5.2	1.6-17.4	0.007
Growth pattern
Expanding (ref)	1.0			1.0
Infiltrating	1.0	0.5-1.8	0.9	0.8	0.4-1.7	0.6
1CD44v6 staining pattern
“Front-positive” (ref)	1.0
“Front-negative”	1.4	0.8-2.6	0.2
Recurrence
No (ref)				1.0
Yes				74.3	17.0-326.7	< 0.001

¹Not significant in univariate analysis and thus not included in multivariate model. Ref: Reference category; HR: Hazard ratio; DFS: Disease-free survival; DSS: Disease-specific survival; CD44v6: CD44 variant 6.